Pyrotinib is an irreversible EGFR/HER2 inhibitor that has been approved for the treatment of breast cancer. The aim of this work was to establish a quantification method for the simultaneous determination of pyrotinib and its metabolite pyrotinib-lactam in rat plasma using UPLC-MS/MS. After simple protein precipitation with acetonitrile, the analytes and internal standard (neratinib) were separated on an ACQUITY BEH C₁₈ column (2.1 × 50 mm, 1.7 μm) using a mobile phase of water containing 0.1% formic acid and acetonitrile. The detection was performed using selected reaction monitoring mode with precursor-to-product ion transitions at m/z 583.2 > 138.1 for pyrotinib, m/z 597.2 > 152.1 for pyrotinib-lactam, and m/z 557.2 > 112.1 for internal standard. The assay exhibited excellent linearity in the concentration range of 0.5–1000 ng/mL for pyrotinib and pyrotinib-lactam. The assay met the criteria of the United States Food and Drug Administration–validated bioanalytical methods and was successfully applied to a pharmacokinetic study of pyrotinib and its metabolite for the first time. Our results demonstrated that pyrotinib rapidly converted into pyrotinib-lactam, whose in vivo exposure was 21% that of pyrotinib.

中文翻译：

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UPLC-MS/MS 测定同时测定大鼠血浆中的吡罗替尼及其氧化代谢物：在药代动力学研究中的应用

吡罗替尼是一种不可逆的 EGFR/HER2 抑制剂，已被批准用于治疗乳腺癌。本工作的目的是建立一种使用 UPLC-MS/MS 同时测定大鼠血浆中吡罗替尼及其代谢物吡罗替尼-内酰胺的定量方法。用乙腈进行简单的蛋白质沉淀后，在 ACQUITY BEH C ₁₈色谱柱（2.1 × 50 mm，1.7 μm）上使用含有 0.1% 甲酸和乙腈的水作为流动相分离分析物和内标物（neratinib）。检测是使用选定的反应监测模式进行的，其中前体到产物的离子跃迁对于吡罗替尼为m/z 583.2 > 138.1，对于吡罗替尼 - 内酰胺为m/z 597.2 > 152.1，以及m/z内标为 557.2 > 112.1。该测定在 0.5–1000 ng/mL 的浓度范围内对吡罗替尼和吡罗替尼-内酰胺表现出极好的线性。该测定符合美国食品和药物管理局验证的生物分析方法的标准，并首次成功应用于吡罗替尼及其代谢物的药代动力学研究。我们的结果表明，吡罗替尼迅速转化为吡罗替尼-内酰胺，其体内暴露量是吡罗替尼的 21%。